1. Adaptive Immune System Chapter 16

2. Overview of Adaptive Immunity
Adaptive immunity is the body’s ability to recognize and defend itself against distinct invaders and their products
Five attributes of adaptive immunity
1. _______________
Any adaptive response acts against only one particular molecule shape and not others.
Specific pathogens
2. _______________
Activation of adaptive cells only in response to specific pathogens 2

3. Five attributes of adaptive immunity continued..
3. _____________
Once induced cells of the adaptive system proliferate (expand) to form many generations of nearly identical cells (clones).
4. _____________________________
The adaptive system does not act against normal body cells.
5. __________________________
An adaptive immune response has memory which allows a quick response if you encounter the pathogen again

4. Innate vs. adaptive Innate Adaptive Nonspecific response
A fever is a fever whether triggered by a cold virus or Ebola
Always ready and fast acting
Born with these systems
Adaptive
Specific immune response to a pathogen
If you have a cold virus antibodies are produced specifically for that virus
Slower
Not born with an adaptive system
Antibodies can be transferred through breast milk

5. Types of Acquired Immunity
Specific immunity acquired during an individual’s life
_________________
Distinguished as either active or passive
Active- normal exposure and response to pathogen
Passive immunity
Receive antibodies from another individual
Newborns respond slowly to antigen
IgG crosses the placenta providing protection
IgA in breast milk-
____________________ 5

6. Dual Nature of Adaptive Immunity
T and B cells develop from stem cells in red bone marrow
Stem cells develop in bone marrow
Red bone marrow of adults
Differentiate to B cells in adult red bone marrow
Thymus
Differentiate to T cells in thymus
Migrate to lymphoid tissue such as spleen, but especially lymph nodes

7. Dual Nature of Adaptive Immunity
Two types of adaptive immune responses

8. Where does the Adaptive Immune response take place?
The Tissues and Organs of the Lymphatic System
Act as a surveillance system that screens the tissues of the body for foreign antigens
Composed of lymphatic vessels and lymphatic cells, tissues, and organs 8

9. The Nature of Antigens
Include various bacterial components as well as proteins of viruses, fungi, and protozoa
Food and dust can also contain antigenic particles

10. Types of antigens Derived from normal cell processes
Extracellular microbes
Exogenous antigens
Toxins and other secretions
Components of cell walls, membranes, flagella
Endogenous antigens are not accessible to immune cells
Immune cells will respond if the endogenous antigen is incorporated into the bodies cells cytoplasmic membranes (external display)
Derived from normal cell processes
Endogenous antigens
Intracellular virus
Virally infected cell
Autoantigens (normal cell antigens)
Normal (uninfected) cell

11. The Nature of Antibodies
Globular proteins called immunoglobulin's
Secreted by _____________________
Antibodies (Ab) interact with________________ _______________

12. antigenic determinants on antigen
Epitopes (antigenic determinants).
Antibody A
antigenic determinants on antigen
Antigens: components of cell wall
Binding sites
Bacterial cell
Antibody B

13. Antibodies Classes of antibodies ____–first antibody produced
____–most common (80% of serum antibodies) and longest-lasting antibody
____– associated with body secretions, provides nursing newborns some protection against foreign antigens, newborn receives antibodies against antigens that have infected their mothers
_____–involved in response to parasitic infections and allergies
_____–exact function is not known 13

14. Humoral Response The introducing the players: Extra cellular antigen
B cells
BCRs
T helper cells (T-dependent humoral immunity only)
CD4
MHC class II proteins
Exogenous antigen processing
Cytokines (chemical signalling)

15. B Cells and Antibodies Arise and mature in the red bone marrow
Found primarily in the spleen and lymph nodes
Small percentage of B cells circulates in the blood 15

16. B Cells and Antibodies
The process leads to the secretion of antibodies starts when B cells are exposed to extracellular antigens.
B cells carry immunoglobulin's on surface of cell
Called B cell receptors (BCRs)
Each B lymphocyte has multiple copies of the same B cell receptor
Each B cell generates a single BCR
~500,000 identical copies per cell
Billions of different BCR’s in a human

17. Figure 16.4 B cell receptor (BCR)
Epitope
Antigen- binding sites
Heavy chain
Variable region
Light chain
Cytoplasmic membrane of B lymphocyte
Transmembrane portion of BCR
B cell receptor (BCR)
Cytoplasm

18. T Cells T Helper lymphocyte T cells mature in the thymus
Have T cell receptors (TCRs) on their cytoplasmic membrane
TCRs do not recognize epitopes directly
TCRs only bind epitopes associated with a MHC protein
Have either CD 4 or CD 8 protein (to recognize MHC)
T Helper lymphocyte
T helper cells require ______________________ _____________________

19. The Roles of the Major Histocompatibility Complex (MHC)
Major histocompatibility antigens are proteins found in the membranes of most cells of vertebrate animals

20. The Roles of the Major Histocompatibility Complex (MHC)
Antigens bind to MHC molecules
Two classes of MHC proteins
_______________Found on every nucleated cell
_______________Found only on B cells and antigen presenting cells (APC)
Antigen-binding grooves
Cytoplasmic membrane
Class I MHC on every nucleated cell
Class II MHC on B cell or other antigen-presenting cell (APC) 20

21. Antigen Presenting Cells (APC) and Antigen Processing
Digest antigen
Display antigen fragments on APC surface with MHC
Exogenous Antigen processing
Antigen presenting cells internalize the antigen and digest the in the phagolysosome
A vesicle containing MHC II fuses with the phagolysosome and the antigens can bind to its complementary MHC II molecule

22. Role of CD4
T helper cells recognize antigens presented with their ______and _____protein on T helper recognizes _____________
T helpers become activated when antigen is presented on a MHC II and matches its ______

23. Complex of MHC class II molecule and antigen fragment
Exogenous Processing
An APC encounters, in this case a B cell, and ingests a microorganism. The antigen is enzymatically processed into short peptides, which combine with MHC class II molecules and are displayed on the surface of the APC.
A receptor (TCR) on the surface of the T helper cell (TH cell) binds to the MHC–antigen complex. The APC is stimulated to secrete a costimulatory molecule. These two signals activate the TH cell, which produces cytokines.
TH cell receptor (TCR)
The cytokines cause the TH cell to become activated.
B cell
T helper cell
Antigen
Complex of MHC class II molecule and antigen fragment
Cytokines
Antigen fragment (short peptides)
Microorganism carrying antigens
Costimulatory molecule, (required to activate T cells that have not previously encountered antigen)

24. Humoral Immune Responses
Two types
________________humoral immunity 24

25. T-dependent humoral immunity
The process
T-dependent
Antigen is presented with __________to TH cell
TH cell produces _________that activate the B cell
Once B cell is activated the B cell undergoes _____ _____________________
B cells differentiate into:

26. Clonal selection and differentiation of B cells.
Stem cell
Stem cells differentiate into mature B cells, each bearing surface immunoglobulins against a specific antigen.
Antigen
B cells
B cell III complexes with its specific antigen and proliferates. I II
III IV
Memory cells
Some B cells proliferate into long-lived memory cells, which at a later date can be stimulated to become antibody-producing plasma cells. See Figure
Other B cells proliferate into antibody-producing plasma cells.
Plasma cells
Plasma cells secrete antibodies into circulation.
Antigens in circulation now attached to circulating antibodies
Cardiovascular system

27. T-dependent humoral response worksheet

28. T-independent humoral immunity
When a molecule with ________________ ____________________________the BCRs on a B cell
1. The B cell is activated
2. undergoes clonal expansion
3. the clones become plasma cells which secrete antibodies

29. (T-independent antigen)
T-independent humoral immunity
Polysaccharide
(T-independent antigen)
Epitopes
B cell receptors

30. T-independent humoral response worksheet

31. Humoral Immune Responses
Memory B Cells and the Establishment of Immunological Memory
Produced by B cell proliferation but do not secrete antibodies
Have BCRs complementary to the antigenic determinant that triggered their production
Long-lived cells that persist in the lymphoid tissue
Initiate antibody production if antigen is encountered again 31

32. Outcomes of Antigen–Antibody Binding

33. The results of antigen–antibody binding.
PROCTECTIVE MECHANISM OF BINDING ANTIBODIES TO ANTIGENS
Agglutination
Activation of complement
Reduces number of infectious units to be dealt with
Causes inflammation and
cell lysis
Complement
Bacteria
Bacterium
Lysis
Opsonization
Antibody-dependent
cell-mediated cytotoxicity
Coating antigen with antibody enhances phagocytosis
Antibodies attached to target cell cause destruction by macrophages, eosinophils, and NK cells
Phagocyte
Eosinophil
Epitopes
Large target cell (parasite)
Neutralization
Perforin and lytic enzymes
Blocks adhesion of bacteria and viruses to mucosa
Blocks attachment of toxin
Virus
Toxin
Bacterium

35. Cell mediated response
The Players
Intracellular antigen (virally infected cells)
T cytotoxic cells (Tc)
Cytotoxic T lymphocytes (CTLs)
CD8
T helper cells
APCs
Macrophages
Dendritic cells
MHC class I

36. T Cells and Cell Mediated Immunity
T cytotoxic cells (Tc)
Have ______________which recognize Endogenous antigen packaged with ___________protein on _____ ________________________________
Produce perforins and granzyme
Directly kills infected cells
Tc and CTLs require antigen-presenting cells with MHC class I

37. Antigen presenting cells (APC)
Macrophages
Dendritic cells- “scouts” most important!
Found under surface of skin and mucous membranes
After acquiring antigen they will migrate to lymph nodes to interact with B and T cells

38. A dendritic cell.

39. Antigen Processing
Endogenous – from pathogens living within a cell the antigen is broken down and packaged inside the cell with MHC I and displayed on the cell surface
Processed antigen
MHC class I
Virus-infected cell (example of endogenous antigen)
Virus-infected cell
Processed antigen presented with
Virus
Virus-infected cell 39

40. Cell-Mediated Immune Responses
See worksheet or next 3 slides explain process 40

41. Cell-Mediated Immune Responses
Steps involved in activation of CTL’s (see worksheet)
Antigen presentation- an APC (usually dendritic cell) presents antigen on a MHC class I protein to Tc cells (T cytotoxic cells)
The one with matching TCR binds to dendritic cell
CD8 on Tc cell recognizes MHC I
Helper T cell stimulates Tc cell -A T helper cell will provide a signal to the Tc to undergo differentiation into a CTL and clonal expansion 41

42. Steps involved in activation of CTL’s
Differentiation- the signal from the Th cell causes the Tc cell to differentiate into a CTL
Clonal expansion- CTLs reproduce to form memory T cells and CTL clones
Self-stimulation- the clonal CTLs cells no longer need an APC or helper T cell, they will signal themselves and leave the lymph node ready to attack virally infected cells

43. Steps involved in activation of CTL’s
Activated CTLs with their TCRs and CD8 will recognize virally infected cells with endogenous antigen packaged with MHC class I, since viral antigens are presented on the cytoplasmic membrane
CTLs will bind to the infected cell with its TCR and complementary MHC I/antigen complex
Once bound the CTL kills their target
By activating apoptotic factors
Perforin and granzymes

44. Figure 16.15b A cell-mediated immune response: perforin-granzyme cytotoxic pathway
Tc cell
Perforin
Granzyme
Perforin complex (pore)
Inactive apoptotic enzymes
Granzymes activate apoptotic enzymes
Active apoptotic enzymes induce apoptosis
Virally infected cell

45. Apoptosis.

46. Natural Killer (NK) Cells
Granular leukocytes destroy cells that don’t express MHC I
Kill virus-infected and tumor cells
Attack parasites

47. Immunological Memory
Primary response occurs after initial contact with Ag
Secondary (memory) response occurs after second exposure

48. Figure 16.19 The production of primary and secondary humoral immune responses--overview